WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205480
CAS#: 1086062-66-9
Description: Omipalisib, also known as GSK2126458, is a small-molecule pyridylsulfonamide inhibitor of phosphatidylinositol 3-kinase (PI3K) with potential antineoplastic activity. PI3K inhibitor GSK2126458 binds to and inhibits PI3K in the PI3K/mTOR signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability and inducing apoptotic cell death. Bax is a member of the proapoptotic Bcl2 family of proteins. PI3K, often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
MedKoo Cat#: 205480
Name: Omipalisib
CAS#: 1086062-66-9
Chemical Formula: C25H17F2N5O3S
Exact Mass: 505.10202
Molecular Weight: 505.5
Elemental Analysis: C, 59.40; H, 3.39; F, 7.52; N, 13.85; O, 9.50; S, 6.34
Synonym: GSK2126458; GSK-2126458; GSK 2126458; Omipalisib
IUPAC/Chemical Name: 2,4-difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide
InChi Key: CGBJSGAELGCMKE-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H17F2N5O3S/c1-35-25-23(32-36(33,34)24-5-3-18(26)12-21(24)27)11-17(13-29-25)15-2-4-22-20(10-15)19(7-8-28-22)16-6-9-30-31-14-16/h2-14,32H,1H3
SMILES Code: O=S(C1=CC=C(F)C=C1F)(NC2=CC(C3=CC=C4N=CC=C(C5=CC=NN=C5)C4=C3)=CN=C2OC)=O
Appearance: light yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Omipalisib (GSK2126458) is an orally active and highly selective inhibitor of PI3K and has anti-cancer activity. Omipalisib has Kis of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM for p110α/β/δ/γ, mTORC1/2, respectively. |
| In vitro activity: | Many dual catalytic mTOR inhibitors do not have tolerable clinical profiles, [14] so this study investigated a clinically acceptable dual PI3K/mTOR inhibitor omipalisib (GSK2126458) [15] that has completed a Phase 1 clinical trial in patients with advanced solid tumors [16] and another Phase 1 trial in patients with idiopathic pulmonary fibrosis [17]. Cell lines were grown in DMEM media (Corning, Manassas, VA, USA) supplemented with 100 U/mL penicillin, 100 μg/mL streptomycin (Gibco, Gaithersburg, MA, NY, USA), 10 mM glutamine, and 10% fetal bovine serum (FBS) (Atlanta Biologicals, Atlanta, GA, USA) and were maintained at 37 °C in a humidified atmosphere with 5% CO2. Omipalisib (GSK2126458) was obtained from MedKoo Sciences (Morrisville, NC, USA). Stocks were made in DMSO (Sigma-Aldrich, St. Louis, MO, USA) 1–100 mM and stored in aliquots at −20 °C, prior to appropriate dilution for inhibition studies.The PI3K/mTOR inhibitor effectively reduced phosphorylation of S6, 4E-BP1, Akt and, in an additive manner with rapamycin, inhibited cell growth. Our study demonstrated that omipalisib dose-dependently inhibits pAkt and both mTORC1 protein synthetic pathways and, in an additive manner with rapamycin, inhibited the growth of TSC2-null cells. Omipalisib, or another inhibitor of both major mTORC1 growth pathways and pAkt, might provide therapeutic options for TSC2-deficient cancers including, but not limited to, LAM.We suggest that a clinically tolerable PI3K/mTOR inhibitor might be beneficial in LAM, as monotherapy or in combination with rapamycin, and in other mTORC1-driven neoplastic diseases. Biomolecules. 2020 Jan; 10(1): 28.Published online 2019 Dec 24. doi: 10.3390/biom10010028 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022412/ |
| In vivo activity: | This study aimed to investigate the antineoplastic effects of omipalisib and its underlying molecular mechanisms in ESCC using a high throughput screen. MTT assay and clone formation were used to determine cell viability and proliferation. Flow cytometry was conducted to detect cell cycle distribution and apoptosis. Global gene expression and mRNA expression levels were determined by RNA sequencing and real-time PCR, respectively. Protein expression was evaluated in the 4 ESCC cell lines by Western blot analysis. Finally, a xenograft nude mouse model was used to evaluate the effect of omipalisib on tumor growth in vivo. In the pilot screening of a 1404-compound library, we demonstrated that omipalisib markedly inhibited cell proliferation in a panel of ESCC cell lines. Mechanistically, omipalisib induced G0/G1 cell cycle arrest and apoptosis. RNA-seq, KEGG, and GSEA analyses revealed that the PI3K/AKT/mTOR pathway is the prominent target of omipalisib in ESCC cells. Treatment with omipalisib decreased expression of p-AKT, p-4EBP1, p-p70S6K, p-S6, and p-ERK, therefore disrupting the activation of PI3K/AKT/mTOR and ERK signaling. In the nude mouse xenograft model, omipalisib significantly suppressed the tumor growth in ESCC tumor-bearing mice without obvious adverse effects. Med Sci Monit. 2020; 26: e927106-1–e927106-13.Published online 2020 Aug 17. Prepublished online 2020 Aug 11. doi: 10.12659/MSM.927106 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450785/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.0 | 19.8 |
The following data is based on the product molecular weight 505.5 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Rønnow SR, Dabbagh RQ, Genovese F, Nanthakumar CB, Barrett VJ, Good RB, Brockbank S, Cruwys S, Jessen H, Sorensen GL, Karsdal MA, Leeming DJ, Sand JMB. Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis. Respir Res. 2020 May 7;21(1):108. doi: 10.1186/s12931-020-01369-1. PMID: 32381012; PMCID: PMC7203825. 2. Evans JF, Rue RW, Mukhitov AR, Obraztsova K, Smith CJ, Krymskaya VP. Inhibition of Growth of TSC2-Null Cells by a PI3K/mTOR Inhibitor but Not by a Selective MNK1/2 Inhibitor. Biomolecules. 2019 Dec 24;10(1):28. doi: 10.3390/biom10010028. PMID: 31878201; PMCID: PMC7022412. 3. Zhu DS, Dong JY, Xu YY, Zhang XT, Fu SB, Liu W. Omipalisib Inhibits Esophageal Squamous Cell Carcinoma Growth Through Inactivation of Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK Signaling. Med Sci Monit. 2020 Aug 17;26:e927106. doi: 10.12659/MSM.927106. PMID: 32804918; PMCID: PMC7450785. 4. Wong K, Di Cristofano F, Ranieri M, De Martino D, Di Cristofano A. PI3K/mTOR inhibition potentiates and extends palbociclib activity in anaplastic thyroid cancer. Endocr Relat Cancer. 2019 Apr 1;26(4):425-436. doi: 10.1530/ERC-19-0011. Epub 2019 Jan 1. PMID: 30699064; PMCID: PMC6602869. |
| In vitro protocol: | 1. Rønnow SR, Dabbagh RQ, Genovese F, Nanthakumar CB, Barrett VJ, Good RB, Brockbank S, Cruwys S, Jessen H, Sorensen GL, Karsdal MA, Leeming DJ, Sand JMB. Prolonged Scar-in-a-Jar: an in vitro screening tool for anti-fibrotic therapies using biomarkers of extracellular matrix synthesis. Respir Res. 2020 May 7;21(1):108. doi: 10.1186/s12931-020-01369-1. PMID: 32381012; PMCID: PMC7203825. 2. Evans JF, Rue RW, Mukhitov AR, Obraztsova K, Smith CJ, Krymskaya VP. Inhibition of Growth of TSC2-Null Cells by a PI3K/mTOR Inhibitor but Not by a Selective MNK1/2 Inhibitor. Biomolecules. 2019 Dec 24;10(1):28. doi: 10.3390/biom10010028. PMID: 31878201; PMCID: PMC7022412. |
| In vivo protocol: | 1. Zhu DS, Dong JY, Xu YY, Zhang XT, Fu SB, Liu W. Omipalisib Inhibits Esophageal Squamous Cell Carcinoma Growth Through Inactivation of Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK Signaling. Med Sci Monit. 2020 Aug 17;26:e927106. doi: 10.12659/MSM.927106. PMID: 32804918; PMCID: PMC7450785. 2. Wong K, Di Cristofano F, Ranieri M, De Martino D, Di Cristofano A. PI3K/mTOR inhibition potentiates and extends palbociclib activity in anaplastic thyroid cancer. Endocr Relat Cancer. 2019 Apr 1;26(4):425-436. doi: 10.1530/ERC-19-0011. Epub 2019 Jan 1. PMID: 30699064; PMCID: PMC6602869. |
GSK2126458 is a highly potent PI3K and mTOR inhibitor. In vivo, GSK2126458 showed anti-tumor activity in both pharmacodynamic and tumor growth efficacy models. GSK2126458 reduced the phosphorylated AKT, p70S6K contents in a dose and time dependent way. The IC50 of GSK2126458 is 2 nM for pAKT in the HCC1954 breast carcinoma cell line. In various human tumor cells, GSK2126458 had a width of inhibitory activity for potent cell growth and induced cell death. Notably, GSK2126458 acted mainly by not induction of apoptosis but cell cycle arrest, particularly in G1-phase
